Bcl-xL is an important anti-apoptotic protein that belongs to the bcl-2 family. Bcl-xL is a critical determinant of intimal lesion formation and thus is an important contributor to the progression of vascular disease. Pollman et al. (1998) Nature Medicine 4: 222–227. In addition, bcl-xL has been implicated as a causative factor in cancer.
The subject invention involves oligonucleotides that reduce or eliminate the expression of bcl-xL. Synthetic oligodeoxynucleotides have been utilized as antisense inhibitors of mRNA translation in vitro and in vivo. Beaucage, S., and Caruthers, M., (1981) Tetrahedron Lett. 37:3557; Iverson, P. (1991) Anti-Cancer Drug Des. 6:531; Ratajczak, et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89:11823; Uhlmann, E., and Peyman, A. (1990) Chem. Rev. 90:544–579. Antisense oligonucleotides have found widespread application because of their abilities to control and/or inhibit gene expression in a selective manner in cellular systems. Ghosh, S., et al. (1990) J. Biol. Chem. 265:2935–2940; Hemken, P., et al. (1992) J. Biol. Chem. 267:9948–0057; Lestinger, R., U.S. Pat. No. 4,958,103, issued Sep. 18, 1990; Shewmaker et al., U.S. Pat. No. 5,107,065, issued Apr. 21, 1992; Tullis, U.S. Patent No., issued Jun. 11, 1991; Zhao, Q., et al. (1993) Antisense Research and Development 3:53–66. Thus, the subject invention represents a precise and selective way of regulating bcl-xl expression both in vivo and in vitro.